Requires 2 weeks of symptoms (considered a syndrome) No objective test for depression Limited understanding of pathophysiology --several brain systems involved Wide range of symptomatology: depressed irritable mood anhedonia weight changes, sleep changes psychomotor agitation fatigue worthlessness guilt diminished concentration suicidal ideation / bx

Antidepressants Flashcards by Nikos Rebetis

Pharmacological Treatment of Depression: General

50% of all patients are tx-resistant to AD’s

All classes of AD’s work on the same/ similar neural pathways, but wide range of symptoms (syndrome) suggests large variance in individual neurochemistry

Limited neural area of effect of AD’s may explain the high rates of failure

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Disorders treated with Antidepressants

Anxiety disorders

Depressive disorders

Personality Disorders

Schizoaffective Disorder

Eating Disorders

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Antidepressant Selection

Most AD efficacy is similar

Selection is based on:

past response hx
side effect profile
coexisting medical conditions

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Depression, General

Requires 2 weeks of symptoms (considered a syndrome)

No objective test for depression

Limited understanding of pathophysiology –several brain systems involved

Wide range of symptomatology:

depressed irritable mood
anhedonia
weight changes,*
sleep changes
psychomotor agitation
fatigue
worthlessness
guilt*
diminished concentration
suicidal ideation / bx

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Biological theories of depression

Permissive hypothesis
● Depleted 5-HT increases NE

Catecholamine thoery: decreased NE

Indolamine theory: decreased 5-HT

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Tricyclics (TCA)

5-HT and NE reuptake inhibition

Very effective but can have serious side effects

Lethal in overdose
*even 1-week supply can be lethal

Also indicated for neuropathic pain and migraines

E.g.
Imipramine (Tofranil, developed 1951)
Clomiprimine (Anafranil, effective for OCD)

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Selective Serotonin Reuptake Inhibitors (SSRIs)

Block presynaptic serotonin reuptake

Similar therapeutic benefits as MAOIs and TCAs, but fewer side effects

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SSRI: Paroxetine (Paxil): Pro’s

Short half-life, with no active metabolite
*no long-term build-up

Sedation helps with sleep disturbances

Well absorbed in GI tract, good for patients with absorption problems

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Monoamine Oxidase Inhibitors (MAOIs)

Inhibit MAO-A enzyme from being created
*Preventing breakdown of NE, DA, 5-HT

*Very effective for depression

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MAOI Side Effects

Weight gain

Dry mouth

Sedation

Sexual dysfunction

Sleep disturbances

Orthostatic hypotension

Serotonin syndrome

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MAOI food restrictions

Tyramine leads to hypertensive crisis by increasing the release of norepinephrine (NE)

MAO-A is inhibited and NE levels get too high, leading to dangerous increases in blood pressure (hypertension)

Foods to avoid:
Aged meats and cheeses
soy sauce
draft beer
wine 
avocados

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MAOI Indications

Currently used with treatment-resistant patients
[* = non-responsive to at least 3 separate treatments]

e.g. Nardil, Parnate

More effective at treating atypical depression

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SSRI: Sertraline (Zoloft) Pro’s

Less sedating

Lower risk of P450 interactions

Short half life with lower build-up of metabolites

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SSRI: Fluoxetine (Prozac) Pros:

Long half-life
*decreased risk of overdose and withdrawal

Initially activating, may provide increased energy

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SSRI: Citalopram (Celexa) Pro’s:

Fewest drug interactions of all SSRIs

Intermediate half-life lowers risk of discontinuation syndrome

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SNRI’s: Serotonin-Norepinephrine Reuptake Inhibitors

e.g. Effexor, Cymbalta

SNRI’s commonly used to treat:

major depression
anxiety
neuropathic pain

Function similarly to TCAs but without antihistamine, antiadrenergic, and anticholinergic side effects

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SNRI: Venlafaxine (Effexor) Pro’s

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Effexor:

Short half life and fast renal clearance avoids build-up *good for geriatric populations

High therapeutic success rate
*effective for treatment-resistant depression

Quick onset of antidepressant and anxiolytic activity

Minimum interactions

SNRI: Duloxetine (Cymbalta) Pro’s:

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Cymbalta:

Effective in elderly patients with recurrent MDD

AD effects may be noticed after one week

**Less BP increase than Effexor

Reduces painful physical symptoms of depression

Low risk of weight gain

Lower rate of sexual side effects vs SSRIs

Low risk hypomania, mania, or hypomanic-like symptoms

Novel/Atypical Antidepressants: Remeron: Indications

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Remeron:

MDD, but not a first-line drug

*Good choice for people with depression, anxiety, and insomnia (off label tx of insomnia)

Novel/Atypical Antidepressants: Bupropion (Wellbutrin/Zyban): General

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Wellbutrin (NDRI):

Popular as augmenting agent for first-line SSRI

Also used as a second or third-line ADHD tx

Selective Serotonin Reuptake Enhancers (SSREs)

e.g. Coaxil

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Opposite mechanism of SSRI

SSRE reduces 5-HT levels

5-HT and DA inversely related

MDD tx: decrease 5-HT to increase DA

Norepinephrine Reuptake Inhibitors (NRI or NERI)

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Lower abuse potential than stimulants

Strattera: ADHD

Edronax: MDD

SSRI’s: Common Side effects

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GI complaints

Anxiety, Restlessness, Insomnia

Sedation, Fatigue, Dizziness

Sexual dysfunction (30% chance)

Less Common:
Low risk of cardiotoxicity in overdose

SSRI’s: Discontinuation Syndrome

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Agitation

Nausea

Disequilibrium

Dysphoria

Serotonin syndrome

Group of mild to severe symptoms that may occur following use of certain serotonergic medications or drugs: High body temperature Agitation Increased reflexes Tremor Sweating Dilated pupils Diarrhea

TCA's: Side Effects

Lethal in overdose Anticholinergic effects Q-T interval prolongation *Slows down blood flow through the heart

Common Anticholinergic Side Effects

Blurred vision Constipation Decreased sweating Dizziness Dry mouth Difficulty urinating and/or kidney failure

Future of Antidepressants

Since 1950s, all antidepressants/anti-anxiety medications attempt to alter DA, 5-HT, NE Anxiety and Depression are both linked with increased activation in the HPA axis *excessive release of the corticotrophin-releasing hormone or factor (CRF) Current push to discover medications that act as CRF-antagonists

Antidepressants: Delayed Onset

Often a 3-6 week delay before sx improvement after tx dose is achieved *Likely due to 2nd messenger process

SSRI: Paroxetine (Paxil): Cons

**Contraindicated in Pregnancy** Weight gain Increased risk of drug interaction More prone to discontinuation symptoms

Atypical Depression

Increased sensitivity to loss Dysthymia Limbs feeling heavy Melancholic depression (weight / sleep disturbances) *Treated with MAOI's (e.g. Nardil, Parnate)

SSRI: Sertraline (Zoloft): Cons:

Zoloft Cons: Requires full stomach Strong GI disruptions

SSRI: Fluoxetine (Prozac) Cons:

Prozac Cons: Long half-life may cause buildup Significant drug-drug interactions May increase anxiety and insomnia More likely to induce mania

SSRI: Citalopram (Celexa) Cons:

Celexa Cons: GI issues May cause initial anxiety May be overly sedating Affects cardiovascular health

SNRI: Venlafaxine (Effexor) Cons:

Effexor Cons: * Hypertension * High rate of tx-emergent mania and hypomania Nausea and Increased GI effects Short half-life: Withdrawal sx possible after missing a single dose More toxic than SSRIs in overdose

SNRI: Duloxetine (Cymbalta) Cons:

Cymbalta Cons: Nausea, sedation, Insomnia May cause severe withdrawal symptoms Patients with preexisting liver disease or excessive alcohol use are at a greater risk of liver injury Unstable absorption rate a fraction of a dose is taken

Novel/Atypical Antidepressants: | Mirtazapine (Remeron) Pros:

Remeron Pro's: Good for severe depression and insomnia *Indicated for depressed geriatric population who show failure to thrive and marked weight loss Selective effects on serotonin receptors *good augmentation strategy for SSRI's

Novel/Atypical Antidepressants: | Mirtazapine (Remeron) Cons:

Remeron Cons: Significant weight gain and sedation Increases cholesterol Beneficial effects decrease as dosage increases May cause agranulocytosis

Novel/Atypical Antidepressants: | Bupropion (Wellbutrin/Zyban) Pro's:

Wellbutrin (NDRI) Pro's: Less weight gain Less sexual dysfunction Less sedation or cardiac risks Little risk of inducing mania

Novel/Atypical Antidepressants: Bupropion (Wellbutrin/Zyban) Cons:

Wellbutrin Cons: Cost: $75-$100 per day Increased risk of seizure *can’t be used with TBI, bulimia, or anorexia Interactions with TCAs Can increase anxiety, agitation, and insomnia Abuse potential, can induce psychosis in high dosages

Non-response to AD, considerations

If no improvement after at least 2months at adequate dose: * switch to another antidepressant * or augment with another agent

Antidepressants Flashcards

(41 cards)